The proposed work concerns the chemical mechanism and physiological control of key enzymes involved in the de novo biosynthesis of fatty acids in living organisms. Pyruvate dehydogenase and fatty acid synthetase are multienzyme complexes subject to a variety of hormonal and nutritional controls. The latter enzyme is composed of two half-size subcomplexes active in a number of partial reactions. We hope to delineate the mechanism for the coordinate control of these enzymes and the spatial arrangement and enzymatic properties of polypeptides comprising fatty acid synthetase. Malic enzyme functions to provide reducing equivalents for fatty acid synthesis. It is a bifunctional enzyme catalyzing both NADP+ -linked hydride transfer and C-C bond cleavage reactions. We are studying the structure-function relationship of this enzyme by characterizing essential -SH and histidyl groups at or near the active site of this enzyme, as well as the role of divalent metal in the catalytic reaction. BIBLIOGRAPHIC REFERENCES: 1. Tang, C.L. and Hsu, R.Y. (1974). Mechanism of Pigeon Liver Malic Enzyme. Modification of Sulfhydryl Groups by 5,5'-Dithiobis-(2-Nitrobenzoic Acid) and N-Ethyl Maleimide. J. Biol. Chem. 249, 3916. 2. Bratcher, S.C. and Hsu, R.Y. (1975). Separation of Active Enzyme Components from the Fatty Acid Synthetase of Chicken Liver. Biochim. Biophys. Acta. 410, 229.